Genetic Variant KRTAP4-4:p.Gln89Gln (chr17-41160425-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_032524.2(KRTAP4-4):c.267A>G(p.Gln89Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000346 in 1,389,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

KRTAP4-4
NM_032524.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.762

Variant links:

Genes affected

KRTAP4-4 (HGNC:16928): (keratin associated protein 4-4) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

KRTAP4-4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-41160425-T-C is Benign according to our data. Variant chr17-41160425-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647761.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.762 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-4	NM_032524.2 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 1 of 1	ENST00000390661.5	NP_115913.1	Q9BYR3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-4	ENST00000390661.5 link	c.267A>G	p.Gln89Gln	synonymous_variant	Exon 1 of 1	6	NM_032524.2	ENSP00000375076.3		Q9BYR3

Frequencies

GnomAD3 genomes

AF:

0.0000433

AC:

AN:

69210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000896

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000302

AC:

AN:

232066

Hom.:

AF XY:

0.0000316

AC XY:

AN XY:

126628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000350

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000561

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000341

AC:

AN:

1319808

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

656242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000419

Gnomad4 OTH exome

AF:

0.0000195

GnomAD4 genome

AF:

0.0000433

AC:

AN:

69210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33752

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000896

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000627

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KRTAP4-4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.56

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over